Study on carbon monoxide toxicity independent of hypoxia

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1. Carbon monoxide (CO) poisoning caused by CO exposure at 3000 ppm for 40 min stimulated hydroxyl radical (・OH) generation in rat striatum.(1) The CO-induced ・OH generation was suppressed by a voltage-dependent Na^+ channel blocker, tetrodotoxin (TTX).(2) CO poisoning increased the extracellular glutamate (Glu) level, but Glu receptor antagonists (MK-801 and NBQX) had no effect on the ・OH generation.(3) α-Methyl-p-tyrosine, clorgyline (Inhibitors of DA synthesis and oxidative metabolism, respectively) and dexamethazone 21-phosphate (a phospholipase A2 inhibitor) had no effect on the CO-induced ・OH generation.(4) Nitric oxide (NO) synthase inhibitors and an NO precursor, L-arginine (L-Arg), and its enantiomer, D-Arg, had complex effects on the CO-induced ・OH generation. (This might be at least partly due to the nature of the striatum that may have a low ability to enhance NO production by utilising exogenous L-Arg.)(5) The CO-induced ・OH generation was more slowly induced by the CO poisoning in the absence of extracellular Cat than in the presence of extracellular Ca^<2+>. The ・OH generation in the absence of extracellular Ca^<2+> was suppressed by dantrolene (an inhibitor of Ca^<2+> release from sarcoplasmic reticulum).(6) Hypoxic hypoxia (HH; 5% O_2 for 40 min) stimulated ・OH generation in the striatum, though more wearly than the CO poisoning.2. CO (3000 ppm for 40 min) and HH (5% O_2 for 40 min) induced similar changes in O_2 contents and oxyhemoglobin levels, but not pO_2, in arterial blood and extracellular amino acids (Glu, taurine and alanine), the blood flow and pO_2 in the striatum.